title: Rapid access to halohydrofurans via Brønsted acid-catalyzed hydroxylation/halocyclization of cyclopropyl methanols with water and electrophilic halides.
abstract: A one-pot, two-step method to prepare 3-halohydrofurans efficiently by TfOH-catalyzed hydroxylation/halocyclization of cyclopropyl methanols with H(2)O and N-halosuccinimide (NXS, X=1, Br, Cl) or Selectfluor is described. The reactions proceed rapidly under mild and operationally straightforward conditions with a catalyst loading as low as 1 mol % and afford the 3-halohydrofuran products in moderate to excellent yields and, in most cases, with preferential cis diastereoselectivity. The method was shown to be applicable to cyclopropyl methanols containing electron-withdrawing, electron-donating, and sterically demanding functional groups and electrophilic halide sources. The mechanism is suggested to involve protonation of the alcohol substrate by the Brønsted acid catalyst and ionization of the starting material. This results in ring-opening of the cyclopropane moiety and in situ formation of a homoallylic alcohol intermediate, which undergoes subsequent intramolecular halocyclization on treating with the electrophilic halide source to give the halohydrofuran. The observed cis product selectivity is thought to be determined by the reaction proceeding through an in situ generated unsaturated alcohol intermediate that contains a (Z)-alkene moiety under the kinetically controlled conditions.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
authors.forename: Srinivasa Reddy
authors.initials: SR
authors.lastname: Mothe
authors.forename: Prasath
authors.initials: P
authors.lastname: Kothandaraman
authors.forename: Weidong
authors.initials: W
authors.lastname: Rao
authors.forename: Philip Wai Hong
authors.initials: PW
authors.lastname: Chan
mesh_terms: D000438:Alcohols / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis*; D002384:Catalysis; D003521:Cyclopropanes / Q000737:chemistry*; D004583:Electrons; D005663:Furans / Q000138:chemical synthesis*; D006219:Halogens / Q000737:chemistry*; D006900:Hydroxylation; D000432:Methanol / Q000031:analogs & derivatives* / Q000737:chemistry; D011522:Protons; D013237:Stereoisomerism; D013388:Succinimides / Q000737:chemistry; D014867:Water
chemical_list: D000438:Alcohols; D000475:Alkenes; D001688:Biological Products; D003521:Cyclopropanes; D005663:Furans; D006219:Halogens; D011522:Protons; D013388:Succinimides; C490695:cyclopropylcarbinol; D014867:Water; C032620:succinimide; C030797:cyclopropane; D000432:Methanol